title: Association of host genetic risk factors with the course of cytomegalovirus retinitis in patients infected with human immunodeficiency virus.
abstract: OBJECTIVE
  To evaluate the effects of previously reported host genetics factors that influence cytomegalovirus (CMV) retinitis incidence, progression to acquired immune deficiency syndrome (AIDS), and efficacy of highly active antiretroviral therapy (HAART) for mortality, retinitis progression, and retinal detachment in patients with CMV retinitis and AIDS in the era of HAART.
  
  
  METHODS
  Prospective, multicenter, observational study.
  
  
  METHODS
  Cox proportional hazards model based genetic association tests examined the influence of IL-10R1_S420L, CCR5-Δ32, CCR2-V64I, CCR5 promoter, and SDF-3'A polymorphisms among patients with mortality, retinitis progression, and retinal detachment. Participants were 203 European-American and 117 African-American patients with AIDS and CMV retinitis.
  
  
  RESULTS
  European-American patients with the CCR5 +.P1.+ promoter haplotype showed increased risk for mortality (hazard ratio [HR] = 1.83; 95% confidence interval [CI]: 1.00-3.40; P = .05). Although the same haplotype also trended for increased risk for mortality in African-American patients, the result was not significant (HR = 2.28; 95% CI: 0.93-5.60; P = .07). However, this haplotype was associated with faster retinitis progression in African Americans (HR = 5.22; 95% CI: 1.54-17.71; P = .007). Increased risk of retinitis progression was also evident for African-American patients with the SDF1-3'A variant (HR = 3.89; 95% CI: 1.42-10.60; P = .008). In addition, the SDF1-3'A variant increased the retinal detachment risk in this patient group (HR = 3.05; 95% CI: 1.01-9.16; P = .05).
  
  
  CONCLUSIONS
  Besides overall immune health, host genetic factors influence mortality, retinitis progression, and retinal detachment in patients with AIDS and CMV retinitis that are receiving HAART.
authors.affiliation: Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702, USA. efe.sezgin@nih.gov
authors.forename: Efe
authors.initials: E
authors.lastname: Sezgin
authors.forename: Mark L
authors.initials: ML
authors.lastname: van Natta
authors.forename: Alka
authors.initials: A
authors.lastname: Ahuja
authors.forename: Alice
authors.initials: A
authors.lastname: Lyon
authors.forename: Sunil
authors.initials: S
authors.lastname: Srivastava
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Troyer
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Jabs
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D044383:Black People / Q000235:genetics; D018791:CD4 Lymphocyte Count; D054377:Chemokine CXCL12 / Q000235:genetics*; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D053709:Interleukin-10 Receptor alpha Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D012307:Risk Factors; D019562:Viral Load; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C515334:CCR2 protein, human; D054377:Chemokine CXCL12; D053709:Interleukin-10 Receptor alpha Subunit; D054390:Receptors, CCR2; D019713:Receptors, CCR5